S306: HYPERCOAGULABILITY BIOMARKERS AND THROMBIN GENERATION (TG) PREDICT VENOUS THROMBOEMBOLISM (VTE) IN METASTATIC LUNG CANCER PATIENTS
Authors: Patricia Gomez Rosas, Marina Marchetti, Cinzia Giaccherini, Laura Russo, Sara Gamba, Cristina Verzeroli, Carmen Julia Tartari, Silvia Bolognini, Francesca Schieppati, Chiara Ticozzi, Roberta Sarmiento, Luigi Celio, Giovanna Masci, Carlo Tondini, Fausto Petrelli, Francesco Giuliani, Andrea D’alessio, Filippo De Braud, Armando Santoro, Roberto Labianca, Giampietro Gasparini, Anna Falanga
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: VTE is a common complication in lung cancer patients and is associated with an increased mortality. The tight and reciprocal interaction between cancer and hemostasis led us to investigate the role of hemostatic biomarkers in the prediction of cancer associated thrombosis. Aims: In a large prospective cohort of metastatic lung cancer patients, we assessed whether hemostatic biomarkers and TG can predict for VTE and mortality within the first 6 months after diagnosis (HYPERCAN study, Clinical Trials.gov ID# NCT02622815). The Khorana risk score (KRS), a validated VTE risk prediction model, was also utilized to assess the VTE risk and mortality in the same cohort of patients. Methods: 568 newly diagnosed patients with metastatic lung cancer, and a median age of 65 years (range: 34-88) were studied. Platelet-free plasma samples were tested for factor VIII (FVIII), D-dimer, fibrinogen, prothrombin fragment 1 + 2 [F1 + 2], proteins C and S, and TG by the calibrated automated thrombogram at 5pM tissue factor (TF). Clinical data were recorded at enrollment, VTE and death were monitored during follow-up. Results: During follow-up, 63 patients experienced a VTE, which consisted of 30 isolated pulmonary embolism (PE), 27 deep vein thrombosis (DVT), and 9 PE + DVT, providing a 6-months cumulative incidence of 12% (11-18). Patients who developed a VTE during follow-up were characterized by increased baseline levels of D-dimer (p=0.002), FVIII (p=0.007), F1 + 2 (0.002) and peak of TG (p=0.002), as well as shorter lag time and time to peak (p<0.05) of TG, compared with patients without VTE. The remaining hemostatic parameters were similar between the two groups. During the same follow-up, 158 deaths occurred, with a cumulative incidence of 31% (27-35). By competitive multivariate Fine–Gray proportional hazard regression model (with death as competing risk), D-dimer, F1 + 2 levels, and peak of TG were identified as independent risk factors (p<0.05) for VTE. Based on the sub-distribution HR of the 3 biomarkers, we generated a continuous risk-score for the prediction of VTE. By ROC analysis, a value of 850 was identified as the best cut-off of the score (AUC 0.648, p= 0.001) for the stratification of patients in a high and a low-risk category of VTE. According to this cut-off, the cumulative incidence of VTE was 5.8% (0.32-12.9) in the low-risk group, and 14% (12-20) in the high-risk group. No significant stratification of patients in different VTE risk categories was obtained by the application of the KRS. Differently, the KRS significantly stratified the patients at different risk of death, providing cumulative incidences of 22%, 32%, and 49% in the low-, intermediate-, and high-risk categories, respectively (p<0.05), and of 22% vs 37% (p<0.001) in the low- vs high-risk group by the single 2-point cut-off value. Finally, we found that VTE occurrence was associated with a higher risk of death (VTE vs no VTE: 42 vs 28%; log-rank <0.001). Summary/Conclusion: Our data show the important contribution of hemostatic biomarkers in the identification of metastatic lung cancer patients at higher risk of VTE, where the KRS failed to provide significant results. In addition, our study provides evidence that cancer patients with VTE had significantly lower survival rates than those without and identifies the predictive ability of the KRS for mortality in patients with lung cancer. Keywords: Hypercoagulation, Venous thromboembolism, Lung cancer, D-dimer